Composition for ameliorating peripheral sensory neuropathy

ABSTRACT

No drug has been available for treating a peripheral sensory neuropathy caused as a side effect by a drug, in particular, by an anticancer drug such as oxaliplatin. 
     A composition for ameliorating peripheral sensory neuropathy, which is characterized by including a Lentinus edodes mycelium extract, ameliorates symptoms induced by the drug such as the anticancer drug, including numbness of extremities, a pain in extremities, a reduction in deep tendon reflection, a reduction in muscle force, allodynia, hyperalgesia, impaired finger fine movement, impaired walking, stumbling, falling, impaired flexion (being difficult or impossible to sit on one&#39;s heels, sit cross-legged, sit with one&#39;s legs out to one side, sit on a chair, or the like), or paralysis of extremities.

FIELD

The present invention relates to an amelioration composition forrelieving, alleviating, or preventing a peripheral sensory neuropathy,and in particular, a composition for ameliorating the peripheral sensoryneuropathy caused by an anticancer drug.

BACKGROUND

Drugs with various action mechanisms have been developed to be used in achemotherapy for a malignant tumor. These drugs inhibit survival orproliferation of the tumor cell on the basis of specific actionmechanisms. However, in general, these drugs not only act on the tumorcell, but also give the similar effect on a normal cell. Thus, takingthe drug used in the chemotherapy causes a side effect such as hairloss, vomiting, a digestive tract disorder, hepatotoxicity,nephrotoxicity, and neurotoxicity along with the effect of inhibitingthe tumor. Thus, a side-effect relieving drug for relieving these sideeffects has been demanded.

For example, Patent literature 1 discloses that cilnidipine or apharmaceutically acceptable salt thereof relieves an organopathy causedby an anthracycline-based anticancer drug (adriamycin).

Further, Patent literature 2 discloses that an ingredient extracted froma mixture of a culture liquid in which the Lentinus edodes is culturedand a Lentinus edodes mycelium ameliorates symptoms of bone marrowtoxicity caused by cyclophosphamide and 5-fluorouracil, hair loss and adigestive tract disorder caused by cytosine arabinoside, and a renaldisorder induced by cisplatin.

CITATION LIST Patent Literature

Patent Literature 1: Japanese Patent Application Laid-Open No.2013-014549

Patent Literature 2: Japanese Patent Application Laid-Open No. Hei.11-158080

SUMMARY Technical Problem

The side effects of the drugs such as the anticancer drug cause manycommon symptoms, however, some symptoms are specific to the drugs.Administration of a DNA replication inhibitor (a platinum-basedanticancer drug (oxaliplatin, etc.) and an alkylating agent), amicrotubule-stabilizing agent (paclitaxel, etc.), a microtubulepolymerization inhibitor (vincristine, etc.), or a proteasome inhibitor(bortezomib, etc.) causes a peripheral sensory neuropathy such asallodynia, hyperesthesia, or hypoesthesia as the side effect. Thesesymptoms are specifically caused by the aforementioned drugs.

In particular, the peripheral sensory neuropathy is often developed witha symptom of a sensory neuropathy and causes a paresthesia accompaniedby a spontaneous pain and an intense pain. A steady occurrence of such asymptom undesirably puts a stop to administration of the anticancer drugwhich has been therapeutically effective and impairs the quality ofdaily life of the patient, thus posing a significant problem. Further,no effective therapy for the peripheral sensory neuropathy induced bythese anticancer drugs has yet been established to date.

Solution to Problems

The present invention has been conceived in view of the foregoingproblems and provides a composition for ameliorating peripheral sensoryneuropathy that ameliorates a side effect, namely, a peripheral sensoryneuropathy induced by a drug such as an anticancer drug includingoxaliplatin and paclitaxel.

More specifically, the composition for ameliorating the peripheralsensory neuropathy induced by the anticancer drug or the like accordingto the present invention is characterized by including a Lentinus edodesmycelium extract.

Advantageous Effects of Invention

The present invention can provide the composition for amelioratingperipheral sensory neuropathy. That is, administration of the Lentinusedodes mycelium extract can ameliorate a disorder induced by the cancerchemotherapy or the like such as numbness of extremities, a pain inextremities, a reduction in deep tendon reflection, a reduction inmuscle force, allodynia, hyperalgesia, impaired finger fine movement,impaired walking, stumbling, falling, impaired flexion (being difficultor impossible to sit on one's heels, sit cross-legged, sit with one'slegs out to one side, sit on a chair, or the like), or paralysis ofextremities.

In order to manage the peripheral sensory neuropathy, it has been forcedto reduce the amount of the anticancer drug or discontinue thechemotherapy until now. Using the composition of the present inventionmakes it possible to continue the appropriate cancer treatment, therebyleading to an early recovery from the cancer.

Further, the present invention, which provides the orally administrablecomposition for ameliorating peripheral sensory neuropathy that can beeasily administered at home, is extremely convenient for the patientundergoing the cancer treatment at home. Further, the quality of life ofthe patient can be improved by ameliorating the peripheral sensoryneuropathy caused by the cancer chemotherapy.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram illustrating a result of a von Frey test in which acomposition for ameliorating peripheral sensory neuropathy according tothe present invention is coadministered with oxaliplatin.

FIG. 2 is a diagram illustrating a result of a cold plate test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is coadministered with oxaliplatin.

FIG. 3 is a diagram illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is coadministered with paclitaxel.

FIG. 4 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is coadministered with paclitaxel.

FIG. 5 is a diagram illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is coadministered with vincristine.

FIG. 6 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is coadministered with vincristine.

FIG. 7 is a diagram-illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is coadministered with bortezomib.

FIG. 8 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is coadministered with bortezomib.

FIG. 9 is a diagram illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is administered after administration ofoxaliplatin.

FIG. 10 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is administered after administrationof oxaliplatin.

FIG. 11 is a diagram illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is administered after administration ofpaclitaxel.

FIG. 12 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is administered after administrationof paclitaxel.

FIG. 13 is a diagram illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is administered after administration ofvincristine.

FIG. 14 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is administered after administrationof vincristine.

FIG. 15 is a diagram illustrating a result of the von Frey test in whichthe composition for ameliorating peripheral sensory neuropathy accordingto the present invention is administered after administration ofbortezomib.

FIG. 16 is a diagram illustrating a result of the cold plate test inwhich the composition for ameliorating peripheral sensory neuropathyaccording to the present invention is administered after administrationof bortezomib.

DESCRIPTION OF EMBODIMENTS

The composition for ameliorating peripheral sensory neuropathy accordingto the present invention will be described below with reference to thedrawings and examples. The following description exemplifies anembodiment and an example of the present invention, and the presentinvention is not limited to the following description. The followingdescription may be modified without departing from the spirit of thepresent invention.

There is no particular limitation on “Lentinus edodes mycelium” servingas a raw material of a Lentinus edodes mycelium extract used in thecomposition for ameliorating peripheral sensory neuropathy according tothe present invention. For example, a mycelium on the stage preceding afruit body used as food can be used. In the present invention, forexample, an extract obtained by culturing a Lentinus edodes in a solidmedium (the Lentinus edodes mycelium extract) can be used. In theamelioration composition according to the present invention, the term“amelioration” not only means a radical treatment, but also means aneffect of relieving, alleviating, or preventing a side effect caused byan anticancer drug or the like during the administration period.

The Lentinus edodes mycelium extract used in the composition forameliorating peripheral sensory neuropathy according to the presentinvention can be prepared by a known method in the technical field,however, an extract obtained by crushing the mycelium, followed byextraction, can be used. Further, for example, an extract obtained bycrushing and decomposing the solid medium including the mycelium in thepresence of water can be used. As a solvent used for preparing theextract, for example, water, ethanol, methanol, butanol, isopropanol,and the like can be used. Water can be preferably used. The extractioncan be performed by heating the solvent (e.g., about 85 to 105° C.),however, the extraction can be also performed at a lower temperature(e.g., 25 to 50° C., preferably 30 to 45° C.) by an ultrasonictreatment.

As the “Lentinus edodes mycelium extract”, for example, an extractobtained by the following method can be used, although not limitedthereto. That is, the Lentinus edodes is seeded on a solid medium havingbagasse (a dry residue of sugarcane) and defatted rice bran as basematerials. Next, the solid medium including the mycelia obtained bygrowing the mycelium is disentangled such that the amount of the 12-meshpassing disentangled solid medium becomes not more than 30 wt %. Thedisentangled solid medium was added with water and then crushed andgrinded while being maintained at a temperature of 30 to 55° C., so thatat least 70 wt % or more of the bagasse fibers pass through the 12-meshsieve. Next, the 12-mesh passing products are heated to a temperature of80° C., and a suspension-like liquid thus obtained is filtered to obtaina Lentinus edodes mycelium extract liquid.

In the present invention, the extract liquid obtained in this manner maybe used as the Lentinus edodes mycelium extract as it is. However, forconvenience, the extract liquid is concentrated and freeze dried, andstored as a powder, and such a powder is served in a variety of formswhen used. The powder obtained by freeze drying is brown, hygroscopicand has a peculiar taste and odor.

The Lentinus edodes mycelium extract thus obtained contains 15 to 50%,preferably 20 to 40% (w/w) carbohydrates determined by carbohydrateanalysis using the phenol-sulfuric acid method. Further, it contains 10to 40%, preferably 13 to 30% (w/w) proteins determined by proteinanalysis using the Lowry method. Further, it contains 1 to 5%,preferably 2.5 to 3.5% (w/w) polyphenols determined by the Folin-Denismethod using gallic acid as a standard. In addition to those, theLentinus edodes mycelium extract contains about 0.1% fats, about 0.4%fibers, and about 20% ashes.

Further, an example of the constituting sugar composition (mass %) ofthe Lentinus edodes mycelium extract obtained as described above is asfollows. Note that this composition may vary depending on cultureconditions and the like. Xylose: 15.2; arabinose: 8.2; mannose: 8.4;glucose: 39.4; galactose: 5.4; amino sugar (glucosamine): 12.0; uronicacid: 11.3.

The composition for ameliorating peripheral sensory neuropathy accordingto the present invention includes the aforementioned Lentinus edodesmycelium extract. The content ratio of the Lentinus edodes myceliumextract in the composition for ameliorating peripheral sensoryneuropathy is not particularly limited. It can be appropriately changeddepending on a subject to be administered (including an animal) and asymptom (a cause). However, it is desirable that the composition forameliorating peripheral sensory neuropathy includes the Lentinus edodesmycelium extract in an amount of at least 10 mass % or more, preferably20 mass % or more, most preferably 30 mass % or more. The Lentinusedodes mycelium extract in the composition for ameliorating peripheralsensory neuropathy may be 100 mass %.

The composition for ameliorating peripheral sensory neuropathy can beprovided as a therapeutic agent (a medical composition) for theperipheral sensory neuropathy. As the medical composition, thecomposition according to the present invention can exhibit its effect byoral administration. Thus, it can be provided as an internalpreparation. For example, the composition for ameliorating peripheralsensory neuropathy in a power form can be formulated into a capsule, agranule, a powder, a tablet, and the like, and provided. When used as anoral agent, the composition can be added with an additive such as abinder, a lubricant, a disintegrator, a colorant, a flavoring agent, anantiseptic, an antioxidant, and a stabilizer, and the oral agent can beproduced in a form of a capsule, a granule, a powder, and a tablet by aroutine method.

Further, the medical composition according to the present invention maybe formulated into an external preparation such as a liquid, anointment, a cream, a gel, a stick, and an aerosol, and the externalpreparation may be parenterally administered. When used as the externalpreparation, the composition can be compounded with water, a loweralcohol, a solubilizer, a surfactant, an emulsion stabilizer, a gellingagent, an adhesive, and other necessary base ingredients. Further, anadditive such as a vasodilator, adrenocortical hormone, a keratolyticagent, a moisturizing agent, a bactericide, an antioxidant, a refreshingagent, a perfume, and a coloring matter may be appropriately compounded.

It is desirable that the medical composition according to the presentinvention include the Lentinus edodes mycelium extract in an amount ofat least 10 mass % or more, preferably 20 mass % or more, and mostpreferably 30 mass % or more. Further, the Lentinus edodes myceliumextract in the medical composition may be 100 mass %.

Further, the composition for ameliorating peripheral sensory neuropathyaccording to the present invention can be provided as a processed food.That is, the composition for ameliorating peripheral sensory neuropathyaccording to the present invention taken as the processed food exhibitsan effect equivalent to that of the amelioration composition accordingto the present invention.

Examples of the processed food include not only a general processed foodincluding a favorite food and health food such as a candy, chewing gum,jelly, a biscuit, a cookie, a rice cracker, bread, a noodle, a fish/meatpaste product, tea, a refreshing beverage, a coffee beverage, a milkbeverage, a whey beverage, a lactic acid bacteria beverage, yogurt, icecream, and pudding, but also foods with health claims such as foods forspecified health uses and foods with nutrient function claims specifiedin the regulatory system “Foods with Health Claims” by the Ministry ofHealth, Labour, and Welfare, Japan. Furthermore, a dietary supplement (asupplement), feed, a food additive, and the like are also included inthe processed food.

The processed food according to the present invention can be prepared byadding the composition for ameliorating peripheral sensory neuropathy(the Lentinus edodes mycelium extract) in raw materials of theseprocessed foods. It is desirable that the processed food according tothe present invention include the Lentinus edodes mycelium extract in anamount of at least 10 mass % or more, preferably 20 mass % or more, mostpreferably 30 mass % or more.

The intake amount of the composition in the present invention can beappropriately selected depending on the symptom, age, weight, an elapsedtime after onset of symptom, a therapeutic treatment performed together,and the like. In an example of the present invention, in a case where amouse is administered with the anticancer drug in an amount of 6 mg/kgmouse body weight, the daily intake amount of the dried powder of theLentinus edodes mycelium extract effective for ameliorating theperipheral sensory neuropathy is 0.02 g (that is, 1.0 g/kg mouse bodyweight considering that the average body weight of mice is 20 g).

In the technical field, it is known that, when an ingredient iseffective in mice, the effective amount of the ingredient expressed asper kg body weight corresponds to an effective dose ingested per day bya human adult male weighing 60 kg. Further, the dose of the anticancerdrug in human is generally one third to equal to the dose of theanticancer drug expressed as per kg mouse body weight in the presentexample.

Thus, the effective amount of the dried powder of the Lentinus edodesmycelium extract ingested per day by a human adult male is preferably0.3 g or more, more preferably 0.3 g to 30.0 g/day/adult, mostpreferably 0.6 g to 24.0 g/day/adult. Note that the term “X to Y”described herein refers to a range between “X or more and Y or less”.

Note that the Lentinus edodes mycelium extract according to the presentinvention is administered to a subject to be administered as thecomposition for ameliorating peripheral sensory neuropathy, and thus itmay also be considered as a method for ameliorating the peripheralsensory neuropathy. In this case, the composition for amelioratingperipheral sensory neuropathy may be the Lentinus edodes myceliumextract itself. That is, the composition for ameliorating peripheralsensory neuropathy may be constituted 100% by the Lentinus edodesmycelium extract.

EXAMPLES

<Culture of Lentinus edodes Mycelium>

A medium used for culturing the Lentinus edodes mycelium was prepared byadding an appropriate amount of pure water to a solid medium including80 parts by weight of bagasse and 10 parts by weight of defatted ricebran. The Lentinus edodes mycelium was seeded on this medium and placedin a culture room where the interior temperature and humidity arecontrolled to propagate the mycelium.

<Production of Dried Powder of Lentinus edodes Mycelium Extract>

To the medium in which the Lentinus edodes mycelium was spread, eightequivalents of pure water was added. The medium was crushed, heated to80° C. for 2 hours by a jacket preheater, subjected to liquidcirculation extraction, and then filtered. The filtered extract wasconcentrated so as to obtain a Brix value of 27%±2%. The concentratedextract was sterilized at 135° C. for 15 seconds using an instantaneousheating sterilizer, and the sterilized extract was added with sterilewater so as to adjust the Brix value to 25%±2% and then subjected tofreeze drying. This freeze-dried powder was crushed and then allowed topass through a 42-mesh sieve to obtain the dried powder of the Lentinusedodes mycelium extract.

(Example 1) <Effect on Peripheral Sensory Neuropathy Induced byOxaliplatin in Mice>

The effect of the Lentinus edodes mycelium extract on hyperesthesia suchas allodynia (an intense pain caused by tactile stimulation that usuallydoes not induce the pain) to mechanical stimulation and paresthesia tocold stimulation induced by administration of oxaliplatin as theanticancer drug was examined. Oxaliplatin is a platinum preparation (aplatinum-based anticancer drug) that inhibits DNA replication. TheLentinus edodes mycelium extract was orally administered to mice and thefollowing tests (a cold plate test and a von Frey test) were performed.

(1) Administration of Test Object

Male Balb/c mice of 6 to 7 weeks old were used. The mice were dividedinto three groups: a control group, an oxaliplatin administration group,and an oxaliplatin and Lentinus edodes mycelium extract administrationgroup (oxaliplatin+Lentinus edodes mycelium extract administrationgroup). Oxaliplatin was administered to each mouse once a day at a doseof 6 mg/kg. Further, the Lentinus edodes mycelium extract wasadministered to each mouse once a day at a dose of 2 g/kg.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, and Day 14) for oxaliplatin and daily (from Day 0 toDay 15) for the Lentinus edodes mycelium extract in both the von Freytest and the cold plate test below.

(2) von Frey Test

The mice in the three groups in the above (1) were put in a cage and afilament having a strength of 0.16 g was pressed on the plantar surfaceof the leg to measure the number of times (a score) of avoidanceresponse. The result is shown in FIG. 1.

Referring to FIG. 1, the horizontal axis indicates an elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). The higher number of times of avoidance means thatthe mouse avoids the stimulation by the filament more. Open circles witha solid line represent the control group. Filled circles with a solidline represent the group in which only oxaliplatin was administered.Open squares with a dash line represent the group in which oxaliplatinand the Lentinus edodes mycelium extract were administered. When thedifference with the control group was determined to be significant usinga significance level of 5%, the data were marked by “*”.

In the oxaliplatin administration group (filled circles with a solidline), the avoidance response score significantly increased three daysafter the administration as compared with the control group (opencircles with a solid line). This suggests that the peripheral sensoryneuropathy was developed by the administration of oxaliplatin. On theother hand, the group in which the Lentinus edodes mycelium extract wascoadministered (oxaliplatin+Lentinus edodes mycelium extractadministration group: open squares with a dash line) showed theavoidance response score of the same level as that in the control group.In the oxaliplatin+Lentinus edodes mycelium extract administrationgroup, an increase in the avoidance response score was suppressed ascompared with that in the oxaliplatin administration group (filledcircles with a solid line).

Further, it was found that, in the oxaliplatin+Lentinus edodes myceliumextract administration group (open squares with a dash line),suppression of the decrease in the pain threshold was continued evenafter finishing the administration of the Lentinus edodes myceliumextract (on Day 16 or later).

(3) Cold Plate Test

The effect of the Lentinus edodes mycelium extract on the paresthesia tocold stimulation was tested by performing the cold plate test. The micein the three groups in the above (1) were put on a cold plate set to 10°C. and a response time for avoidance (a latency) was measured. Theshorter latency means that the mouse avoids the cold stimulation of thecold plate more. The result is shown in FIG. 2.

Referring to FIG. 2, the horizontal axis indicates the elapsed timeafter administration (days) and the vertical axis indicates theavoidance response time (seconds). Open circles with a solid linerepresent the control group. Filled circles with a solid line representthe group in which only oxaliplatin was administered. Open squares witha dash line represent the group in which oxaliplatin and the Lentinusedodes mycelium extract were administered (oxaliplatin+Lentinus edodesmycelium extract administration group). When the difference with thecontrol group was determined to be significant using a significancelevel of 5%, the data were marked by “*”.

On Day 3 in the test, the latency to the cold stimulation of the coldplate was significantly reduced in the oxaliplatin administration group(filled circles with a solid line). This suggests that the peripheralsensory neuropathy was developed by the administration of oxaliplatin.On the other hand, the oxaliplatin+Lentinus edodes mycelium extractadministration group (open squares with a dash line) showed the latencyof about the same level as that in the control group (open circles witha solid line), and thus the decrease in the latency was suppressed ascompared with that in the oxaliplatin administration group (filledcircles with a solid line).

From the above results, it can be concluded that the Lentinus edodesmycelium extract ameliorates the symptom of the peripheral nervouserethism induced by oxaliplatin.

(Example 2) <Effect on Peripheral Sensory Neuropathy Induced byPaclitaxel in Mice>

The effect of the Lentinus edodes mycelium extract of the presentinvention on hyperesthesia such as allodynia to mechanical stimulationand paresthesia to cold stimulation induced by administration ofpaclitaxel as the anticancer drug was examined. Paclitaxel is ataxane-based anticancer drug that inhibits microtubule polymerizationduring cell division by stabilizing a microtubule. The Lentinus edodesmycelium extract of the present invention was orally administered tomice, and the tests (the cold plate test and the von Frey test) wereperformed in the same manner as in Example 1.

(1) Administration of Test Object

Male Balb/c mice of 6 to 7 weeks old were used as in Example 1. The micewere divided into three groups: a control group, a paclitaxeladministration group, and a paclitaxel and Lentinus edodes myceliumextract administration group (paclitaxel+Lentinus edodes myceliumextract administration group). Paclitaxel was administered to each mouseonce a day at a dose of 6 mg/kg. Further, the Lentinus edodes myceliumextract was administered to each mouse once a day at a dose of 2 g/kg.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, and Day 14) for paclitaxel and daily (from Day 0 toDay 15) for the Lentinus edodes mycelium extract in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withoxaliplatin. The result is shown in FIG. 3. Referring to FIG. 3, thehorizontal axis indicates an elapsed time after administration (days)and the vertical axis indicates the avoidance response (scores). Opencircles with a solid line represent the control group. Filled circleswith a solid line represent the group in which only paclitaxel wasadministered. Open squares with a dash line represent the group in whichpaclitaxel and the Lentinus edodes mycelium extract were administered(paclitaxel+Lentinus edodes mycelium extract administration group). Whenthe difference with the control group was determined to be significantusing a significance level of 5%, the data were marked by “*”.

In the paclitaxel administration group (filled circles with a solidline), the avoidance response score significantly increased three daysafter the administration as compared with the control group (opencircles with a solid line). This suggests that the peripheral sensoryneuropathy was developed by the administration of paclitaxel. On theother hand, the group in which paclitaxel and the Lentinus edodesmycelium extract were coadministered (paclitaxel+Lentinus edodesmycelium extract administration group: open squares with a dash line)showed the avoidance response score of the same level as that in thecontrol group. In the paclitaxel+Lentinus edodes mycelium extractadministration group, the increase in the avoidance response score wassuppressed as compared with that in the paclitaxel administration group(filled circles with a solid line).

Further, it was found that, in the paclitaxel+Lentinus edodes myceliumextract administration group (open squares with a dash line),suppression of the decrease in the pain threshold was continued evenafter finishing the administration of the Lentinus edodes myceliumextract (on Day 16 or later).

(3) Cold Plate Test

In the present test, the mice were divided into four groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of four groups,a control group, a paclitaxel administration group, and two differentpaclitaxel and Lentinus edodes mycelium extract administration groups(paclitaxel+Lentinus edodes mycelium extract administration groups).Paclitaxel was administered to each mouse once a day at a dose of 6mg/kg. Further, a group in which the Lentinus edodes mycelium extractwas administered to each mouse once a day at a dose of 1 g/kg(hereinafter referred to as “1 g/kg administration group”) and a groupin which the Lentinus edodes mycelium extract was administered to eachmouse once a day at a dose of 2 g/kg (hereinafter referred to as “2 g/kgadministration group”) were prepared.

Evaluation was performed in the same manner as in the test withoxaliplatin. The result is shown in FIG. 4. Referring to FIG. 4, thehorizontal axis indicates the elapsed time after administration (days)and the vertical axis indicates the avoidance response time (seconds).Open circles with a solid line represent the control group. Filledcircles with a solid line represent the group in which only paclitaxelwas administered. Open squares with a dash line and filled squares witha dash line represent the groups in which paclitaxel and the Lentinusedodes mycelium extract were administered at the same time(paclitaxel+Lentinus edodes mycelium extract administration groups). Theopen squares with a dash line indicate the 1 g/kg administration group,while the filled squares with a dash line indicate the 2 g/kgadministration group. When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

Referring to FIG. 4, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in thepaclitaxel administration group (filled circles with a solid line). Thissuggests that the peripheral sensory neuropathy was developed by theadministration of paclitaxel. On the other hand, the 2 g/kgadministration group (filled squares with a dash line) of thepaclitaxel+Lentinus edodes mycelium extract co-administration groupsshowed the latency of about the same level as that in the control group(open circles with a solid line). Thus, the decrease in the latency wassuppressed in the 2 g/kg administration as compared with that in thepaclitaxel administration group (filled circles with a solid line).

Further, the decrease in the latency was suppressed in the 1 g/kgadministration group (open squares with a dash line) of the groups inwhich paclitaxel and the Lentinus edodes mycelium extract werecoadministered as compared with that in the group in which onlypaclitaxel was administered (filled circles with a solid line).

(Example 3) <Effect on Peripheral Sensory Neuropathy Induced byVincristine in Mice>

The effect of the Lentinus edodes mycelium extract of the presentinvention on hyperesthesia such as allodynia to mechanical stimulationand paresthesia to cold stimulation induced by administration ofvincristine as the anticancer drug was examined. Vincristine inhibitscell mitosis by inhibiting a polymerization reaction of a microtubule.The Lentinus edodes mycelium extract of the present invention was orallyadministered to mice, and the tests (the cold plate test and the vonFrey test) were performed in the same manner as in Example 1.

(1) Administration of Test Object

In the present test, the mice were divided into three groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of three groups,a control group, a vincristine administration group, and a vincristineand Lentinus edodes mycelium extract administration group(vincristine+Lentinus edodes mycelium extract administration group).

Vincristine was administered to each mouse once a day at a dose of 0.2mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, and Day 14) for vincristine and daily (from Day 0 toDay 15) for the Lentinus edodes mycelium extract in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withoxaliplatin in Example 1. The result is shown in FIG. 5. Referring toFIG. 5, the horizontal axis indicates an elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). Open circles with a solid line represent the controlgroup. Filled circles with a solid line represent the group in whichonly vincristine was administered. Open squares with a dash linerepresent the group in which vincristine and the Lentinus edodesmycelium extract were administered at the same time(vincristine+Lentinus edodes mycelium extract administration group).When the difference with the control group was determined to besignificant using a significance level of 5%, the data were marked by“*”.

In the vincristine administration group (filled circles with a solidline), the avoidance response score significantly increased three daysafter the administration as compared with the control group (opencircles with a solid line). This suggests that the peripheral sensoryneuropathy was developed by the administration of vincristine. On theother hand, the vincristine+Lentinus edodes mycelium extractadministration group (open squares with a dash line) showed theavoidance response score of the same level as that in the control group.In the vincristine+Lentinus edodes mycelium extract administrationgroup, the increase in the avoidance response score was suppressed ascompared with that in the vincristine administration group (filledcircles with a solid line).

Further, it was found that, in the vincristine+Lentinus edodes myceliumextract administration group (open squares with a dash line),suppression of the decrease in the pain threshold was continued evenafter finishing the administration of the Lentinus edodes myceliumextract (on Day 15 or later).

(3) Cold Plate Test

In the present test, the mice were divided into three groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of three groups,a control group, a vincristine

administration group, and a vincristine and Lentinus edodes myceliumextract administration group (vincristine+Lentinus edodes myceliumextract administration group).

Vincristine was administered to each mouse once a day at a dose of 0.2mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg.

Evaluation was performed in the same manner as in the test withoxaliplatin in Example 1. The result is shown in FIG. 6. Referring toFIG. 6, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse time (seconds). Open circles with a solid line represent thecontrol group. Filled circles with a solid line represent the group inwhich only vincristine was administered. Open squares with a dash linerepresent the group in which vincristine and the Lentinus edodesmycelium extract were administered at the same time(vincristine+Lentinus edodes mycelium extract administration group).When the difference with the control group was determined to besignificant using a significance level of 5%, the data were marked by“*”.

Referring to FIG. 6, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in thevincristine administration group (filled circles with a solid line).This suggests that the peripheral sensory neuropathy was developed bythe administration of vincristine. On the other hand, thevincristine+Lentinus edodes mycelium extract administration group (opensquares with a dash line) showed the latency of about the same level asthat in the control group (open circles with a solid line). The decreasein the latency was suppressed in the vincristine+Lentinus edodesmycelium extract administration group as compared with that in the groupin which only vincristine was administered (filled circles with a solidline).

(Example 4) <Effect on Peripheral Sensory Neuropathy Induced byBortezomib in Mice>

The effect of the Lentinus edodes mycelium extract of the presentinvention on hyperesthesia such as allodynia to mechanical stimulationand paresthesia to cold stimulation induced by administration ofbortezomib as the anticancer drug was examined. It is known thatbortezomib inhibits proteasome and thus induces apoptosis by inhibitingdegradation of an apoptosis inducing factor. The Lentinus edodesmycelium extract of the present invention was orally administered tomice, and the tests (the cold plate test and the von Frey test) wereperformed in the same manner as in Example 1.

(1) Administration of Test Object

In the present test, the mice were divided into three groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of three groups,a control group, a bortezomib administration group, and a bortezomib andLentinus edodes mycelium extract administration group(bortezomib+Lentinus edodes mycelium extract administration group).

Bortezomib was administered to each mouse once a day at a dose of 1mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, and Day 14) for bortezomib and daily (from Day 0 toDay 15) for the Lentinus edodes mycelium extract in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withoxaliplatin in Example 1. The result is shown in FIG. 7. Referring toFIG. 7, the horizontal axis indicates an elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). Open circles with a solid line represent the controlgroup. Filled circles with a solid line represent the group in whichonly bortezomib was administered. Open squares with a dash linerepresent the group in which bortezomib and the Lentinus edodes myceliumextract were administered at the same time (bortezomib+Lentinus edodesmycelium extract administration group). When the difference with thecontrol group was determined to be significant using a significancelevel of 5%, the data were marked by “*”.

In the bortezomib administration group (filled circles with a solidline), the avoidance response score significantly increased three daysafter the administration as compared with the control group (opencircles with a solid line). This suggests that the peripheral sensoryneuropathy was developed by the administration of bortezomib. Thebortezomib+Lentinus edodes mycelium extract administration group (opensquares with a dash line) showed the avoidance response score of thesame level as that in the control group. In the bortezomib+Lentinusedodes mycelium extract administration group, the increase in theavoidance response score was suppressed as compared with that in thebortezomib administration group (filled circles with a solid line).

Further, it was found that, in the bortezomib+Lentinus edodes myceliumextract administration group (open squares with a dash line),suppression of the decrease in the pain threshold was continued evenafter finishing the administration of the Lentinus edodes myceliumextract (on Day 16 or later).

(3) Cold Plate Test

In the present test, the mice were divided into three groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of three groups,a control group, a bortezomib

administration group, and a bortezomib and Lentinus edodes myceliumextract administration group (bortezomib+Lentinus edodes myceliumextract administration group).

Bortezomib was administered to each mouse once a day at a dose of 1mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg.

Evaluation was performed in the same manner as in the test withoxaliplatin in Example 1. The result is shown in FIG. 8. Referring toFIG. 8, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse time (seconds). Open circles with a solid line represent thecontrol group. Filled circles with a solid line represent the group inwhich only bortezomib was administered. Open squares with a dash linerepresent the group in which bortezomib and the Lentinus edodes myceliumextract were administered at the same time (bortezomib+Lentinus edodesmycelium extract administration groups). When the difference with thecontrol group was determined to be significant using a significancelevel of 5%, the data were marked by “*”.

Referring to FIG. 8, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in thebortezomib administration group (filled circles with a solid line). Thissuggests that the peripheral sensory neuropathy was developed by theadministration of bortezomib. On the other hand, the bortezomib+Lentinusedodes mycelium extract administration group (open squares with a dashline) showed the latency of about the same level as that in the controlgroup (open circles with a solid line). The decrease in the latency wassuppressed in the bortezomib+Lentinus edodes mycelium extractadministration group as compared with that in the group in which onlybortezomib was administered (filled circles with a solid line).

Examples 1 to 4 showed that coadministration of the Lentinus edodesmycelium extract according to the present invention could exhibit theeffect of inhibiting the onset of the peripheral sensory neuropathyinduced by four representative anticancer drugs. Thus, the compositionfor ameliorating peripheral sensory neuropathy including the Lentinusedodes mycelium extract according to the present invention can beconsidered as a composition for preventing peripheral sensory neuropathy(a medical composition for preventing peripheral sensory neuropathy).However, in the actual practice of the cancer treatment, there is a veryhigh demand for a composition for treating peripheral sensory neuropathythat alleviates the symptom of the side effect (the peripheral sensoryneuropathy) once developed.

The Lentinus edodes mycelium extract according to the present inventioncan inhibit (prevent) the onset of the peripheral sensory neuropathywhen coadministered with the anticancer drug. However, the Lentinusedodes mycelium extract according to the present invention can alsoserve as a composition for treating peripheral sensory neuropathy (amedical composition for treating peripheral sensory neuropathy) thatalleviates the peripheral sensory neuropathy once developed. Examplesthereof will be described below.

(Example 5) <Treatment Effect on Peripheral Sensory Neuropathy Inducedby Oxaliplatin in Mice>

The treatment effect of the Lentinus edodes mycelium extract of thepresent invention on hyperesthesia such as allodynia to mechanicalstimulation and paresthesia to cold stimulation induced byadministration of oxaliplatin as the anticancer drug was examined. Theanticancer drug, oxaliplatin, was administered to mice to induce theperipheral sensory neuropathy, and then, the Lentinus edodes myceliumextract of the present invention was orally administered to the mice toperform the same tests (the cold plate test and the von Frey test) asthose in Example 1.

(1) Administration of Test Object

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, an oxaliplatin administration group, two differentoxaliplatin and Lentinus edodes mycelium extract administration groups(oxaliplatin+Lentinus edodes mycelium extract administration groups),and two different oxaliplatin and duloxetine administration groups(oxaliplatin+duloxetine administration groups).

Oxaliplatin was administered to each mouse once a day at a dose of 6mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of oxaliplatin. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively.

Further, groups in which duloxetine was administered after theadministration of oxaliplatin were prepared for comparison. Duloxetine,which is an antidepressant, is applied to a pain accompanied by adiabetic neuropathy and a pain accompanied by fibromyalgia. Duloxetineis sometimes used for the peripheral sensory neuropathy induced by theanticancer drug with a non-opioid or opioid analgesic.

Duloxetine was also administered once a day at a dose of 30 mg/kg threedays or six days after the administration of oxaliplatin. These groupsare referred to as “duloxetine 3-day delayed administration group” and“duloxetine 6-day delayed administration group”, respectively.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, Day 14, and Day 21) for oxaliplatin and daily from theadministration start date (from Day 3 or Day 6 to Day 23) for theLentinus edodes mycelium extract and duloxetine in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withoxaliplatin in Example 1. The result is shown in FIG. 9. Referring toFIG. 9, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). Open circles with a solid line represent the controlgroup. Filled circles with a solid line represent the group in whichonly oxaliplatin was administered. Open squares with a dash line andfilled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of oxaliplatin (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of oxaliplatin (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

The avoidance response score significantly increased in the oxaliplatinadministration group (filled circles with a solid line) as compared withthe control group (open circles with a solid line). As also shown inFIG. 1, this suggests that the peripheral sensory neuropathy wasdeveloped by the administration of oxaliplatin. The Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) had the lower avoidance score than the oxaliplatinadministration group (filled circles with a solid line) after theadministration. The Lentinus edodes mycelium extract 3-day delayedadministration group could maintain the clearly lower value than that inthe oxaliplatin administration group (filled circles with a solid line)on Day 6 or later, if not as low as the control group (open circles witha solid line).

Further, the Lentinus edodes mycelium extract 6-day delayedadministration group (filled squares with a dash line) also maintainedthe clearly lower score than that in the oxaliplatin administrationgroup (filled circles with a solid line) on Day 9 or later. That is, theLentinus edodes mycelium extract administered after the onset of theperipheral sensory neuropathy is still effective for inhibiting thesymptom.

On the other hand, in the duloxetine 3-day delayed administration group(open triangles with a dash line), the avoidance score never becamelower than that in the oxaliplatin administration group (filled circleswith a solid line) after the administration. The duloxetine 3-daydelayed administration group (open triangles with a dash line) hadalmost the same score as that in the oxaliplatin administration group(filled circles with a solid line). Further, the duloxetine 6-daydelayed administration group (filled triangles with a dash line) showedthe same tendency as that in the duloxetine 3-day delayed administrationgroup (open triangles with a dash line). That is, this suggests thatduloxetine does not significantly contribute to the inhibition of theperipheral sensory neuropathy.

It was found that the suppression of the decrease in the pain thresholdwas maintained even after finishing the administration of the Lentinusedodes mycelium extract (Day 23 or later) in the Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) and the Lentinus edodes mycelium extract 6-day delayedadministration group.

(3) Cold Plate Test

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, an oxaliplatin administration group, two differentoxaliplatin and Lentinus edodes mycelium extract administration groups(oxaliplatin+Lentinus edodes mycelium extract administration groups),and two different oxaliplatin and duloxetine administration groups(oxaliplatin+duloxetine administration groups).

Oxaliplatin was administered to each mouse once a day at a dose of 6mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of oxaliplatin. These groups are referred to as“Lentinus edodes mycelium extract 3-day delayed administration group”and “Lentinus edodes mycelium extract 6-day delayed administrationgroup”, respectively.

Further, groups in which duloxetine was administered after theadministration of oxaliplatin were prepared for comparison. Duloxetinewas also administered once a day at a dose of 30 mg/kg three days or sixdays after the administration of oxaliplatin. These groups are referredto as “duloxetine 3-day delayed administration group” and “duloxetine6-day delayed administration group”, respectively.

Evaluation was performed in the same manner as in the test withoxaliplatin in Example 1. The result is shown in FIG. 10. Referring toFIG. 10, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse time (seconds). Open circles with a solid line represent thecontrol group. Filled circles with a solid line represent the group inwhich only oxaliplatin was administered. Open squares with a dash lineand filled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of oxaliplatin (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of oxaliplatin (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

Referring to FIG. 10, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in theoxaliplatin administration group (filled circles with a solid line).This suggests that the peripheral sensory neuropathy was developed byoxaliplatin as seen in the von Frey test. The latency in the Lentinusedodes mycelium extract 3-day delayed administration group (open squareswith a dash line) became clearly longer than that in the oxaliplatinadministration group (filled circles with a solid line) after theadministration. The latency in the Lentinus edodes mycelium extract3-day delayed administration group was recovered to the same level asthat in the control (open circles with a solid line) on Day 9 or later.Further, the latency in the Lentinus edodes mycelium extract 6-daydelayed administration group (filled squares with a dash line) alsobecame longer after the administration and was recovered to the samelevel as that in the control (open circles with a solid line) on Day 12.

On the other hand, the latency in the duloxetine 3-day delayedadministration group (open triangles with a dash line) never becamelonger than that in the oxaliplatin administration group (filled circleswith a solid line) after the administration. The latency in theduloxetine 3-day delayed administration group was almost the same asthat in the oxaliplatin administration group (filled circles with asolid line). Further, the duloxetine 6-day delayed administration group(filled triangles with a dash line) showed the same tendency as that inthe duloxetine 3-day delayed administration group (open triangles with adash line). That is, this suggests that duloxetine does notsignificantly contribute to the inhibition of the peripheral sensoryneuropathy (the cold hypersensitivity).

As described above, when used with the anticancer drug (oxaliplatin),the Lentinus edodes mycelium extract according to the present inventioncan not only inhibit the peripheral sensory neuropathy, but also serveas the composition for treating peripheral sensory neuropathy (themedical composition for treating peripheral sensory neuropathy) thatalleviates the symptom of the peripheral sensory neuropathy oncedeveloped.

(Example 6) <Treatment Effect on Peripheral Sensory Neuropathy Inducedby Paclitaxel in Mice>

The treatment effect of the Lentinus edodes mycelium extract of thepresent invention on hyperesthesia such as allodynia to mechanicalstimulation and paresthesia to cold stimulation induced byadministration of paclitaxel as the anticancer drug was examined. Theanticancer drug, paclitaxel, was administered to mice to induce theperipheral sensory neuropathy, and then, the Lentinus edodes myceliumextract of the present invention was orally administered to the mice toperform the same tests (the cold plate test and the von Frey test) asthose in Example 1.

(1) Administration of Test Object

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, a paclitaxel administration group, two differentpaclitaxel and Lentinus edodes mycelium extract administration groups(paclitaxel+Lentinus edodes mycelium extract administration groups), andtwo different paclitaxel and duloxetine administration groups(paclitaxel+duloxetine administration groups).

Paclitaxel was administered to each mouse once a day at a dose of 6mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of paclitaxel. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively. Further, groups in which duloxetine was administered afterthe administration of paclitaxel were prepared for comparison.

Duloxetine was also administered once a day at a dose of 30 mg/kg threedays or six days after the administration of paclitaxel. These groupsare referred to as “duloxetine 3-day delayed administration group” and“duloxetine 6-day delayed administration group”, respectively.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, Day 14, and Day 21) for paclitaxel and daily from theadministration start date (from Day 3 or Day 6 to Day 23) for theLentinus edodes mycelium extract and duloxetine in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withpaclitaxel in Example 1. The result is shown in FIG. 11. Referring toFIG. 11, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). Open circles with a solid line represent the controlgroup. Filled circles with a solid line represent the group in whichonly paclitaxel was administered. Open squares with a dash line andfilled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of paclitaxel (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of paclitaxel (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

The avoidance response score significantly increased in the paclitaxeladministration group (filled circles with a solid line) three day afterthe administration as compared with the control group (open circles witha solid line). This suggests that the peripheral sensory neuropathy wasdeveloped by the administration of paclitaxel. The Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) had the lower avoidance score than that in the paclitaxeladministration group (filled circles with a solid line) after theadministration. The avoidance score in the Lentinus edodes myceliumextract 3-day delayed administration group was recovered to the samelevel as that in the control (open circles with a solid line) on Day 12.Further, the Lentinus edodes mycelium extract 6-day delayedadministration group (filled squares with a dash line) also maintainedthe clearly lower score than that in the paclitaxel administration group(filled circles with a solid line) on Day 12 or later. That is, theLentinus edodes mycelium extract administered after the onset of theperipheral sensory neuropathy is still effective for inhibiting thesymptom.

On the other hand, in the duloxetine 3-day delayed administration group(open triangles with a dash line), the avoidance score never becamelower than that in the paclitaxel administration group (filled circleswith a solid line) after the administration. The duloxetine 3-daydelayed administration group (open triangles with a dash line) hadalmost the same avoidance score as that in the paclitaxel administrationgroup (filled circles with a solid line). Further, the duloxetine 6-daydelayed administration group (filled triangles with a dash line) showedthe same tendency as that in the duloxetine 3-day delayed administrationgroup (open triangles with a dash line). That is, this suggests thatduloxetine does not significantly contribute to the inhibition of theperipheral sensory neuropathy.

It was found that the suppression of the decrease in the pain thresholdwas maintained even after finishing the administration of the Lentinusedodes mycelium extract (Day 23 or later) in the Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) and the Lentinus edodes mycelium extract 6-day delayedadministration group.

(3) Cold Plate Test

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, a paclitaxel administration group, two differentpaclitaxel and Lentinus edodes mycelium extract administration groups(paclitaxel+Lentinus edodes mycelium extract administration groups), andtwo different paclitaxel and duloxetine administration groups(paclitaxel+duloxetine administration groups).

Paclitaxel was administered to each mouse once a day at a dose of 6mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of paclitaxel. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively.

Further, groups in which duloxetine was administered after theadministration of paclitaxel were prepared for comparison. Duloxetinewas also administered once a day at a dose of 30 mg/kg three days or sixdays after the administration of paclitaxel. These groups are referredto as “duloxetine 3-day delayed administration group” and “duloxetine6-day delayed administration group”, respectively.

Evaluation was performed in the same manner as in the test withpaclitaxel in Example 1. The result is shown in FIG. 12. Referring toFIG. 12, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse time (seconds). Open circles with a solid line represent thecontrol group. Filled circles with a solid line represent the group inwhich only paclitaxel was administered. Open squares with a dash lineand filled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of paclitaxel (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of paclitaxel (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

Referring to FIG. 12, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in thepaclitaxel administration group (filled circles with a solid line). Thissuggests that the peripheral sensory neuropathy was developed bypaclitaxel as seen in the von Frey test. The latency in the Lentinusedodes mycelium extract 3-day delayed administration group (open squareswith a dash line) became clearly longer than that in the paclitaxeladministration group (filled circles with a solid line) after theadministration. The latency in the Lentinus edodes mycelium extract3-day delayed administration group (open squares with a dash line) wasrecovered to the same level as that in the control (open circles with asolid line) on Day 15 or later. Further, the latency in the Lentinusedodes mycelium extract 6-day delayed administration group (filledsquares with a dash line) also became longer after the administration.The latency in the Lentinus edodes mycelium extract 6-day delayedadministration group (filled squares with a dash line) was recovered tothe same level as that in the control (open circles with a solid line)on Day 18 or later.

On the other hand, the latency in the duloxetine 3-day delayedadministration group (open triangles with a dash line) never becamelonger than that in the paclitaxel administration group (filled circleswith a solid line) after the administration. The latency in theduloxetine 3-day delayed administration group was almost the same asthat in the paclitaxel administration group (filled circles with a solidline). Further, the duloxetine 6-day delayed administration group(filled triangles with a dash line) showed the same tendency as that inthe duloxetine 3-day delayed administration group (open triangles with adash line). That is, this suggests that duloxetine does notsignificantly contribute to the inhibition of the peripheral sensoryneuropathy (the cold hypersensitivity).

As described above, when used with the anticancer drug (paclitaxel), theLentinus edodes mycelium extract according to the present invention cannot only inhibit the peripheral sensory neuropathy, but also serve asthe composition for treating peripheral sensory neuropathy (the medicalcomposition for treating peripheral sensory neuropathy) that alleviatesthe symptom of the peripheral sensory neuropathy once developed.

(Example 7) <Treatment Effect on Peripheral Sensory Neuropathy Inducedby Vincristine in Mice>

The treatment effect of the Lentinus edodes mycelium extract of thepresent invention on hyperesthesia such as allodynia to mechanicalstimulation and paresthesia to cold stimulation induced byadministration of vincristine as the anticancer drug was examined. Theanticancer drug, vincristine, was administered to mice to induce theperipheral sensory neuropathy, and then, the Lentinus edodes myceliumextract of the present invention was orally administered to the mice toperform the same tests (the cold plate test and the von Frey test) asthose in Example 1.

(1) Administration of Test Object

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, a vincristine administration group, two differentvincristine and Lentinus edodes mycelium extract administration groups(vincristine+Lentinus edodes mycelium extract administration groups),and two different vincristine and duloxetine administration groups(vincristine+duloxetine administration groups).

Vincristine was administered to each mouse once a day at a dose of 0.2mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of vincristine. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively. Further, groups in which duloxetine was administered afterthe administration of vincristine were prepared for comparison.

Duloxetine was also administered once a day at a dose of 30 mg/kg threedays or six days after the administration of vincristine. These groupsare referred to as “duloxetine 3-day delayed administration group” and“duloxetine 6-day delayed administration group”, respectively.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, Day 14, and Day 21) for vincristine and daily from theadministration start date (from Day 3 or Day 6 to Day 23) for theLentinus edodes mycelium extract and duloxetine in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withvincristine in Example 1. The result is shown in FIG. 13. Referring toFIG. 13, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). Open circles with a solid line represent the controlgroup. Filled circles with a solid line represent the group in whichonly vincristine was administered. Open squares with a dash line andfilled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of vincristine (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of vincristine (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

The avoidance response score significantly increased in the vincristineadministration group (filled circles with a solid line) three day afterthe administration as compared with the control group (open circles witha solid line). This suggests that the peripheral sensory neuropathy wasdeveloped by the administration of vincristine. The Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) had the lower avoidance score than that in the vincristineadministration group (filled circles with a solid line) after theadministration. The avoidance score in the Lentinus edodes myceliumextract 3-day delayed administration group (open squares with a dashline) was recovered to the same level as that in the control (opencircles with a solid line) on Day 12. Further, the Lentinus edodesmycelium extract 6-day delayed administration group (filled squares witha dash line) also maintained the clearly lower score than that in thevincristine administration group (filled circles with a solid line) onDay 12 or later. That is, the Lentinus edodes mycelium extractadministered after the onset of the peripheral sensory neuropathy isstill effective for inhibiting the symptom.

On the other hand, in the duloxetine 3-day delayed administration group(open triangles with a dash line), the avoidance score never becamelower than that in the vincristine administration group (filled circleswith a solid line) after the administration. The duloxetine 3-daydelayed administration group (open triangles with a dash line) hadalmost the same score as that in the vincristine administration group(filled circles with a solid line). Further, the duloxetine 6-daydelayed administration group (filled triangles with a dash line) showedthe same tendency as that in the duloxetine 3-day delayed administrationgroup (open triangles with a dash line). That is, this suggests thatduloxetine does not significantly contribute to the inhibition of theperipheral sensory neuropathy.

It was found that the suppression of the decrease in the pain thresholdwas maintained even after finishing the administration of the Lentinusedodes mycelium extract (Day 23 or later) in the Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) and the Lentinus edodes mycelium extract 6-day delayedadministration group.

(3) Cold Plate Test

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, a vincristine administration group, two differentvincristine and Lentinus edodes mycelium extract administration groups(vincristine+Lentinus edodes mycelium extract administration groups),and two different vincristine and duloxetine administration groups(vincristine+duloxetine administration groups).

Vincristine was administered to each mouse once a day at a dose of 0.2mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of vincristine. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively.

Further, groups in which duloxetine was administered after theadministration of vincristine were prepared for comparison. Duloxetinewas also administered once a day at a dose of 30 mg/kg three days or sixdays after the administration of vincristine. These groups are referredto as “duloxetine 3-day delayed administration group” and “duloxetine6-day delayed administration group”, respectively.

Evaluation was performed in the same manner as in the test withvincristine in Example 1. The result is shown in FIG. 14. Referring toFIG. 14, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse time (seconds). Open circles with a solid line represent thecontrol group. Filled circles with a solid line represent the group inwhich only vincristine was administered. Open squares with a dash lineand filled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of vincristine (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of vincristine (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

Referring to FIG. 14, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in thevincristine administration group (filled circles with a solid line).This suggests that the peripheral sensory neuropathy was developed byvincristine as seen in the von Frey test. The latency in the Lentinusedodes mycelium extract 3-day delayed administration group (open squareswith a dash line) became clearly longer than that in the vincristineadministration group (filled circles with a solid line) after theadministration. The latency in the Lentinus edodes mycelium extract3-day delayed administration group (open squares with a dash line) wasrecovered to the same level as that in the control (open circles with asolid line) on Day 9 or later. Further, the latency in the Lentinusedodes mycelium extract 6-day delayed administration group (filledsquares with a dash line) also became longer after the administration,and was recovered to the same level as that in the control (open circleswith a solid line) on Day 18 or later.

On the other hand, the latency in the duloxetine 3-day delayedadministration group (open triangles with a dash line) never becamelonger than that in the vincristine administration group (filled circleswith a solid line) after the administration. The latency in theduloxetine 3-day delayed administration group was almost the same asthat in the vincristine administration group (filled circles with asolid line). Further, the duloxetine 6-day delayed administration group(filled triangles with a dash line) showed the same tendency as that inthe duloxetine 3-day delayed administration group (open triangles with adash line). That is, this suggests that duloxetine does notsignificantly contribute to the inhibition of the peripheral sensoryneuropathy (the cold hypersensitivity).

As described above, when used with the anticancer drug (vincristine),the Lentinus edodes mycelium extract according to the present inventioncan not only inhibit the peripheral sensory neuropathy, but also serveas the composition for treating peripheral sensory neuropathy (themedical composition for treating peripheral sensory neuropathy) thatalleviates the symptom of the peripheral sensory neuropathy oncedeveloped.

(Example 8) <Treatment Effect on Peripheral Sensory Neuropathy Inducedby Bortezomib in Mice>

The treatment effect of the Lentinus edodes mycelium extract of thepresent invention on hyperesthesia such as allodynia to mechanicalstimulation and paresthesia to cold stimulation induced byadministration of bortezomib as the anticancer drug was examined. Theanticancer drug, bortezomib, was administered to mice to induce theperipheral sensory neuropathy, and then, the Lentinus edodes myceliumextract of the present invention was orally administered to the mice toperform the same tests (the cold plate test and the von Frey test) asthose in Example 1.

(1) Administration of Test Object

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, a bortezomib administration group, two differentbortezomib and Lentinus edodes mycelium extract administration groups(bortezomib+Lentinus edodes mycelium extract administration groups), andtwo different bortezomib and duloxetine administration groups(bortezomib+duloxetine administration groups).

Bortezomib was administered to each mouse once a day at a dose of 1mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of bortezomib. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively. Further, groups in which duloxetine was administered afterthe administration of bortezomib were prepared for comparison.

Duloxetine was also administered once a day at a dose of 30 mg/kg threedays or six days after the administration of bortezomib. These groupsare referred to as “duloxetine 3-day delayed administration group” and“duloxetine 6-day delayed administration group”, respectively.

Further, the number of times of administration was set to once a week(on Day 0, Day 7, Day 14, and Day 21) for bortezomib and daily from theadministration start date (from Day 3 or Day 6 to Day 23) for theLentinus edodes mycelium extract and duloxetine in both the von Freytest and the cold plate test below.

(2) von Frey Test

Evaluation was performed in the same manner as in the test withbortezomib in Example 1. The result is shown in FIG. 15. Referring toFIG. 15, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse (scores). Open circles with a solid line represent the controlgroup. Filled circles with a solid line represent the group in whichonly bortezomib was administered. Open squares with a dash line andfilled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of bortezomib (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of bortezomib (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

The avoidance response score significantly increased in the bortezomibadministration group (filled circles with a solid line) three day afterthe administration as compared with the control group (open circles witha solid line). This suggests that the peripheral sensory neuropathy wasdeveloped by the administration of bortezomib. The Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) had the lower avoidance score than that in the bortezomibadministration group (filled circles with a solid line) after theadministration. The avoidance score in the Lentinus edodes myceliumextract 3-day delayed administration group (open squares with a dashline) was recovered to the same level as that in the control (opencircles with a solid line) on Day 12. Further, the Lentinus edodesmycelium extract 6-day delayed administration group (filled squares witha dash line) also maintained the clearly lower score than that in thebortezomib administration group (filled circles with a solid line) onDay 12 or later. That is, the Lentinus edodes mycelium extractadministered after the onset of the peripheral sensory neuropathy isstill effective for inhibiting the symptom.

On the other hand, in the duloxetine 3-day delayed administration group(open triangles with a dash line), the avoidance score never becamelower than that in the bortezomib administration group (filled circleswith a solid line) after the administration. The duloxetine 3-daydelayed administration group (open triangles with a dash line) hadalmost the same score as that in the bortezomib administration group(filled circles with a solid line). Further, the duloxetine 6-daydelayed administration group (filled triangles with a dash line) showedthe same tendency as that in the duloxetine 3-day delayed administrationgroup (open triangles with a dash line). That is, this suggests thatduloxetine does not significantly contribute to the inhibition of theperipheral sensory neuropathy.

It was found that the suppression of the decrease in the pain thresholdwas maintained even after finishing the administration of the Lentinusedodes mycelium extract (Day 23 or later) in the Lentinus edodesmycelium extract 3-day delayed administration group (open squares with adash line) and the Lentinus edodes mycelium extract 6-day delayedadministration group.

(3) Cold Plate Test

In the present test, the mice were divided into six groups by adifference in test objects. As in Example 1, male Balb/c mice of 6 to 7weeks old were used. The mice were divided into a total of six groups, acontrol group, a bortezomib administration group, two differentbortezomib and Lentinus edodes mycelium extract administration groups(bortezomib+Lentinus edodes mycelium extract administration groups), andtwo different bortezomib and duloxetine administration groups(bortezomib+duloxetine administration groups).

Bortezomib was administered to each mouse once a day at a dose of 1mg/kg. Further, the Lentinus edodes mycelium extract was administered toeach mouse once a day at a dose of 2 g/kg three days or six days afterthe administration of bortezomib. These groups are referred to as“Lentinus edodes mycelium 3-day delayed administration group” and“Lentinus edodes mycelium 6-day delayed administration group”,respectively.

Further, groups in which duloxetine was administered after theadministration of bortezomib were prepared for comparison. Duloxetinewas also administered once a day at a dose of 30 mg/kg three days or sixdays after the administration of bortezomib. These groups are referredto as “duloxetine 3-day delayed administration group” and “duloxetine6-day delayed administration group”, respectively.

Evaluation was performed in the same manner as in the test withbortezomib in Example 1. The result is shown in FIG. 14. Referring toFIG. 14, the horizontal axis indicates the elapsed time afteradministration (days) and the vertical axis indicates the avoidanceresponse time (seconds). Open circles with a solid line represent thecontrol group. Filled circles with a solid line represent the group inwhich only bortezomib was administered. Open squares with a dash lineand filled squares with a dash line represent the groups in which theLentinus edodes mycelium extract was administered after theadministration of bortezomib (“Lentinus edodes mycelium extract 3-daydelayed administration group” and “Lentinus edodes mycelium extract6-day delayed administration group”, respectively).

Further, open triangles with a dash line and filled triangles with adash line represent the groups in which duloxetine was administeredafter the administration of bortezomib (“duloxetine 3-day delayedadministration group” and “duloxetine 6-day delayed administrationgroup”, respectively). When the difference with the control group wasdetermined to be significant using a significance level of 5%, the datawere marked by “*”.

Referring to FIG. 14, on Day 3 in the test, the latency to the coldstimulation of the cold plate was significantly reduced in thebortezomib administration group (filled circles with a solid line). Thissuggests that the peripheral sensory neuropathy was developed bybortezomib as seen in the von Frey test. The latency in the Lentinusedodes mycelium extract 3-day delayed administration group (open squareswith a dash line) became clearly longer than that in the bortezomibadministration group (filled circles with a solid line) after theadministration. The latency in the Lentinus edodes mycelium extract3-day delayed administration group (open squares with a dash line) wasrecovered to the same level as that in the control (open circles with asolid line) on Day 12 or later. Further, the latency in the Lentinusedodes mycelium extract 6-day delayed administration group (filledsquares with a dash line) also became longer after the administration,and was recovered to the same level as that in the control (open circleswith a solid line) on Day 12 or later.

On the other hand, the latency in the duloxetine 3-day delayedadministration group (open triangles with a dash line) never becamelonger than that in the bortezomib administration group (filled circleswith a solid line) after the administration. The latency in theduloxetine 3-day delayed administration group (open triangles with adash line) was almost the same as that in the bortezomib administrationgroup (filled circles with a solid line). Further, the duloxetine 6-daydelayed administration group (filled triangles with a dash line) showedthe same tendency as that in the duloxetine 3-day delayed administrationgroup (open triangles with a dash line). That is, this suggests thatduloxetine does not significantly contribute to the inhibition of theperipheral sensory neuropathy (the cold hypersensitivity).

As described above, when used with the anticancer drug (bortezomib), theLentinus edodes mycelium extract according to the present invention cannot only inhibit the peripheral sensory neuropathy, but also serve asthe composition for treating peripheral sensory neuropathy (the medicalcomposition for treating peripheral sensory neuropathy) that alleviatesthe symptom of the peripheral sensory neuropathy once developed.

Example 9

It was suggested that the Lentinus edodes mycelium extract according tothe present invention could potentially ameliorate the symptom of theperipheral sensory neuropathy with Grade 2 or higher in the clinicaltrials for treating the colorectal cancer. The subjects and methods willbe described below.

The subjects were patients undergoing the XELOX therapy as apostoperative adjuvant chemotherapy for colorectal cancer with StageII/III. After randomly allocated, the patients were administered with atablet formulated with LEM (the Lentinus edodes mycelium according tothe present invention) (1,800 mg/day) or a placebo tablet every day for6 months of the postoperative adjuvant chemotherapy. Oxaliplatin (L-OHP)was administered at a dose of 130 mg/m² on the first day of each 8 cyclefor the 6 months.

As an evaluation item, the onset of the side effect, that is, thesymptom of the peripheral sensory neuropathy, was evaluated according tothe criteria of CTCAE ver.4. The safety analysis set included 46 cases(LEM group: 24 cases, placebo group: 22 cases) capable of initiating theprotocol treatment.

Regarding the onset of the symptom of the peripheral sensory neuropathy(PSN) with Grade 2 or higher, the LEM group tended to have a betteroutcome (LEM group: 16.7% and placebo group: 27.3%). Further, regardingthe median time to the onset of PSN with Grade 2 or higher, the LEMgroup tended to have the longer median time (LEM grope: 158 days andplacebo group: 107 days).

From the above results, it can be concluded that the Lentinus edodesmycelium extract ameliorates (prevents and treats) the symptom of theperipheral nervous erethism. Further, it was shown that the effect couldbe exerted at a dose of 1 g/kg/day or more in mice.

INDUSTRIAL APPLICABILITY

The composition for ameliorating peripheral sensory neuropathy accordingto the present invention can be used to relieve, alleviate, or preventthe peripheral sensory neuropathy. Further, the composition can be usedto treat the peripheral sensory neuropathy once developed. Inparticular, the composition can be preferably used to relieve,alleviate, prevent, or treat the peripheral sensory neuropathy caused bytaking the DNA replication inhibitor (the platinum-based anticancer drug(oxaliplatin, etc.) and the alkylating agent), themicrotubule-stabilizing agent (paclitaxel, etc.), the microtubulepolymerization inhibitor (vincristine, etc.), or the proteasomeinhibitor (bortezomib, etc.).

1. A composition for ameliorating peripheral sensory neuropathycomprising a Lentinus edodes mycelium extract.
 2. The composition forameliorating peripheral sensory neuropathy according to claim 1, whereinthe peripheral sensory neuropathy is induced after administration of ananticancer drug.
 3. The composition for ameliorating peripheral sensoryneuropathy according to claim 2, wherein the anticancer drug is at leastone selected from a DNA replication inhibitor, a microtubule-stabilizingagent, a microtubule polymerization inhibitor, and a proteasomeinhibitor.
 4. The composition for ameliorating peripheral sensoryneuropathy according to claim 2, wherein the anticancer drug is aplatinum-based anticancer drug.
 5. A medical composition forameliorating peripheral sensory neuropathy comprising a Lentinus edodesmycelium extract.
 6. A processed food comprising a Lentinus edodesmycelium extract, wherein the processed food ameliorates peripheralsensory neuropathy.
 7. The composition for ameliorating peripheralsensory neuropathy according to claim 3, wherein the anticancer drug isa platinum-based anticancer drug.